Weiler E, Khalil-Manesh F, Gonick H
Division of Nephrology/Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA.
Environ Health Perspect. 1988 Jun;78:113-7. doi: 10.1289/ehp.8878113.
Inhibition of vascular smooth muscle sodium-potassium-activated adenosine triphosphatase (Na-K-ATPase) has been postulated as a central mechanism in enhancing vascular contractility. In the present study, kinetics of inhibition of Na-K-ATPase by lead, ouabain, and natriuretic hormone (NH) was studied in a purified hog cerebral cortex enzyme preparation. Determination of I50 values for lead, ouabain, and NH revealed that NH is the most potent inhibitor of the enzyme system (0.8 x 10(-6) M ouabain equivalents). Kinetic analyses indicated that lead and NH exhibited different inhibitory mechanisms. The inhibition by lead was noncompetitive with respect to potassium and competitive with respect to sodium and MgATP. Natriuretic hormone was noncompetitive with respect to potassium, uncompetitive with respect to MgATP, and exhibited no inhibitory effect with respect to sodium. Synergism between lead and NH in the inhibition of Na-K-ATPase raises the possibility that lead may be a contributory factor in hypertension via this mechanism.
血管平滑肌钠钾激活三磷酸腺苷酶（Na-K-ATPase）的抑制作用被认为是增强血管收缩性的核心机制。在本研究中，我们在纯化的猪脑皮质酶制剂中研究了铅、哇巴因和利钠激素（NH）对Na-K-ATPase的抑制动力学。铅、哇巴因和NH的I50值测定表明，NH是该酶系统最有效的抑制剂（0.8×10⁻⁶ M哇巴因当量）。动力学分析表明，铅和NH表现出不同的抑制机制。铅的抑制作用在钾方面是非竞争性的，在钠和MgATP方面是竞争性的。利钠激素在钾方面是非竞争性的，在MgATP方面是反竞争性的，对钠没有抑制作用。铅和NH在抑制Na-K-ATPase方面的协同作用增加了铅可能通过这种机制成为高血压促成因素的可能性。
